Atherosclerotic lesions in the cardiovascular system range widely in severity from the limited fatty streak to the extensive complicated plaque. Between these two extremes are lesions that are especially vulnerable to disruption at their surface, often leading to thrombosis and vessel occlusion. The non-invasive detection of these lesions in vivo would provide valuable information for guiding appropriate medical and surgical intervention, as well as monitoring drug therapy over time. This project involves integrated studies on atherosclerotic lesions in human carotid arteries, vessels that afford several important experimental advantages, including availability of surgical tissue (number and mass) and relative ease of imaging in vivo. A primary objective of this project is to develop and refine in vivo MRI to a state where it can accurately quantify physical dimensions of carotid atherosclerotic lesions (e.g. residual lumen area, wall thickness, plaque area) at specific sites throughout the vessel. A secondary objective is to develop in vivo MRI to a level where it can detect, discriminate among and possibly quantify specific chemical components of lesions (e.g. calcified, lipid-rich, fibrotic, necrotic and thrombotic areas). These objectives will be pursued through three specific aims: AIM 1 is to differentiate and estimate the major components of carotid lesions based on their MR images acquired in vivo and ex vivo. Their unique combinations of T1, T2, and proton density will be identified and measured using 3D contour plots, parametric imaging, and feature space analysis. AIM 2 will be to quantify carotid lesion components by histologic and morphometric methods, using conventional and microarray tissue techniques, and to use these measures to calibrate corresponding MR images. AIM 3 is to use non-invasive in vivo MRI to monitor the effect of statin therapy on carotid atherosclerotic lesion characteristics in patients with greater than 40 percent stenosis. Data from all slices will be used to generate arterial profiles showing the volume, radial position, and linear location of the plaque. Successful execution of this project should provide valuable non-invasive technology for monitoring the efficacy of medical intervention on atherosclerotic lesions.